The CLCP1 molecule is also referred to as endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN) or discoidin, CUB and LCCL domain containing 2 (DCBLD2), which is a type I membrane protein of 775 amino acids with a single transmembrane region. An isoform of 743 amino acids, which is a splicing variant, has been reported, and it has a substantially identical extracellular functional domain. Back in 1999, Nadadur S. et al. isolated a gene fragment (Non-patent Document 1), and information on most of the amino acid sequence of CLCP1 (positions 106 to 775 in SEQ ID NO: 2) has been disclosed in Japanese Patent Application Kohyo Publication No. (JP-A) 2002-523076 (unexamined Japanese national phase publication corresponding to a non-Japanese international publication). The extracellular domain has as motifs, CUB domain, LCCL domain, and FA58C domain from the N-terminus. Subsequently, it has been reported that CLCP1 is expressed in the vascular smooth muscles of arteries and tunica media of carotid arteries after balloon injury, as well as in cells of coronary arteries and smooth muscles, and that CLCP1 is useful in the cardiovascular field such as for the treatment of restenosis after PTCA or arteriosclerosis (Patent Document 1).
On the other hand, Takahashi et al. (the present inventors) revealed that the CLCP1 molecule is highly expressed in cells of metastatic lung cancer sublines and expressed at a high rate in vivo in lung cancers. Furthermore, Takahashi et al. identified that cancer growth and metastasis was inhibited by constitutively expressing short hairpin RNAs (shRNAs) against CLCP1, which biosynthesize small interference RNAs (siRNAs) inside the cells (see, for example, Non-patent Documents 1 to 4).
The effects described above were demonstrated to be produced by inhibiting the expression of CLCP1 through constitutive expression of shRNAs that biosynthesize siRNAs inside the cells. The homology between mouse and human CLCP1 molecules is about 85% at the amino acid level. However, monoclonal antibodies that specifically bind to the molecule remain unavailable on the market. There is almost no scientific document reporting such monoclonal antibodies. Thus, such antibodies are still poorly understood in terms of their activity, function, and such. Moreover, the utility of the antibodies must await prospective studies.